Table 1.

Outcomes for Cooperative Group Studies

Protocol by Pediatric Brain Tumor Type	Study Hypothesis	Radiation Therapy	Chemotherapy	Planned Duration of Therapy	Accrual (No. of patients)	Age	EFS
Medulloblastoma
Standard risk
A 996123	To determine efficacy of cyclophosphamide-based regimen versus standard regimen	23.4 Gy CSI; 55.8 Gy PF	Weekly VCR during RT; randomly assigned chemotherapy: CDDP/CCNU/VCR v CDDP/Cyclo/VCR	56 weeks	379	3-18 years	81% ± 2.1% (5 year); no difference between chemotherapy arms
SIOP III43	Randomized study to determine the efficacy of RT alone versus chemotherapy + RT	35 Gy CSI; 55 Gy PF	Weekly VCR during RT; carboplatin and VP16 alternating with cyclophosphamide and VP16	6 weeks for RT alone; 20 weeks for RT + chemotherapy	179	3-16 years	67% (5 year); 74.2% (chemotherapy + RT); 59.8%(RT alone)
High risk
POG 903124	Efficacy of pre-RT chemotherapy on the EFS of high-risk medulloblastoma	35.2-44.0 Gy CSI; 53.2-54.4 Gy PF	Three cycles of pre-RT chemotherapy with CDDP/VP16 followed by seven cycles of Cyclo/VCR v same chemotherapy given post-RT	47 weeks	224	3-18 years	68.1% ± 3% (5 year); no difference between the two arms
High-grade glioma
ACNS012640	Temozolomide administered during and after RT will improve EFS compared with historical controls	54.0 Gy	Temozolomide during RT and followed by RT for 10 cycles	50 weeks	107	3 to ≤ 22 years	11% ± 3% (3 year); no improvement
HIT-GBM-C41	Intensive chemotherapy during and after RT, followed by valproate maintenance therapy, will improve OS compared with historical controls	54 Gy	Two cycles of PEV and PEI, respectively, during RT, followed by six cycles of PEI alternating with monthly VCR, followed by continuous valproate maintenance therapy	30 weeks, followed by continuous valproate maintenance therapy	60	3-17 years	OS: 67% ± 10% (1 year) and 63% ± 12% (5 year) for patients with complete resection only; improvement compared with historical controls; no improvement for incomplete resection
Diffuse pontine glioma
ACNS012644	Temozolomide administered during RT and post-RT will improve EFS compared with historical controls	59.4 Gy	Temozolomide during RT and followed by RT for 10 cycles	46 weeks	63	3-21 years	14% ± 5.5% (1 year); no improvement
ACNS022245	Motexafin-gadolinum administered during RT will improve EFS	54 Gy	Motexafin-gadolinium administered with daily RT	6 weeks	60	< 22 years	18% ± 5% (1 year); no improvement
HIT-GBM-C41	Intensive chemotherapy during and after RT, followed by valproate maintenance therapy will improve OS compared with historical controls	59.4 Gy	Two cycles of PEV and PEI, respectively, during RT, followed by six cycles of PEI alternating with monthly VCR, followed by continuous valproate maintenance therapy	30 weeks, followed by continuous valproate maintenance therapy	37	3-17 years	0.40 ± 0.07 years (median ± SD EFS); no improvement compared with control (0.55 ± 0.098 median ± SD EFS)
Low-grade glioma
A 995246	Compare the efficacy of two active chemotherapy regimens for LGG	—	Carbo/VCR v CCNU/procarbazine/TG/VCR	52 weeks	274	< 10 years	45% ± 3.2% (5 year); no difference in the two regimens
Ependymoma
ACNS0121*	Efficacy of conformal RT in ependymoma	59.4 Gy (> 18 months)	Only for patients with subtotal resection	6 weeks	355	> 12 months to < 21 years	62.6 ± 2.7% (5 year); similar to highly selected single-institution series

Abbreviations: Carbo, carboplatin; CCNU, lomustine; CDDP, cisplatin; CSI, craniospinal irradiation; Cyclo, cyclophosphamide; EFS, event-free survival; HIT-GBM-C, arm C of Hirntumor study for GBM; LGG, low-grade glioma; OS, overall survival; PEI, cisplatin, etoposide, and ifosfamide; PEV, cisplatin, etoposide, and vincristine; PF, posterior fossa; RT, radiotherapy; SD, standard deviation; TG, thioguanine; VCR, vincristine; VP16, etoposide.

^*T. Merchant, personal communication, July 2015.